Adjuvant treatment of intermediate-risk endometrial cancer

Author:: Heidi J Gray, MD
Section Editors:: Barbara Goff, MD; Don S Dizon, MD, FACP; Arno J Mundt, MD
Deputy Editor:: Sadhna R Vora, MD

Literature review current through: Jan 2024.

This topic last updated: Oct 30, 2023.

INTRODUCTION — Cancer of the endometrium is the most common gynecologic malignancy in developed and resource-limited countries. Of the many histologic subtypes, endometrioid carcinoma is the most common and typically presents at an early stage with abnormal uterine bleeding. It is generally associated with a good prognosis. Other histologic types of endometrial carcinoma (eg, serous, clear cell) may not present with uterine bleeding and are often diagnosed at more advanced stages. As a result, these other types are associated with a poorer prognosis.

The stage at diagnosis (table 1 and table 2) and histologic subtype of endometrial carcinoma are used to assign risk for recurrent or persistent disease into low-, intermediate-, and high-risk. This review will focus on adjuvant treatment for patients with intermediate-risk endometrial cancer. An overview of endometrial cancer, including clinical features and an approach to diagnosis, and treatment of low- and high-risk and advanced endometrial cancer are discussed separately.

●(See "Overview of resectable endometrial carcinoma".)

●(See "Endometrial carcinoma: Clinical features, diagnosis, prognosis, and screening".)

●(See "Treatment of low-risk endometrial cancer".)

●(See "Management of locoregional recurrence of endometrial cancer".)

CLASSIFICATION

Definition of intermediate risk — After surgical staging is complete, intermediate-risk endometrial cancer is defined as disease that has the following characteristics (algorithm 1):

●Cancer that is not a high-risk histologic type (eg, clear cell, serous, or carcinosarcoma), and is

•Either histologic grade 1 or 2 and invading less than one-half of the myometrium, with lymphovascular invasion;

•Or histologic grade 1 or 2 and invading more than one-half of the myometrium (stage IB) or demonstrating occult cervical stromal invasion (stage II);

•Or histologic grade 3 cancer and invading less than one-half of the myometrium. Note that we consider grade 3 endometrioid carcinoma that invades more than one-half of the myometrium to be high risk. (See "Adjuvant treatment of high-risk endometrial cancers", section on 'Deeply invasive grade 3 endometrioid carcinoma'.)

We do not consider lower uterine segment (LUS) involvement an intermediate-risk factor, in the absence of other high-risk features. Involvement of cancer within the LUS may identify patients at risk for nodal involvement, although whether it represents an independent risk factor for survival is unclear. The approach to patients with LUS and no other risk features is discussed elsewhere. (See "Treatment of low-risk endometrial cancer", section on 'Patients with lower uterine segment involvement'.)

Identifying high-intermediate-risk disease — The adjuvant treatment options for women with intermediate-risk disease include observation or radiation therapy (RT), depending on whether the disease is considered low-intermediate or high-intermediate risk.

A subset of women are considered to have high-intermediate-risk disease based on certain pathologic criteria. The Gynecologic Oncology Group (GOG) criteria define high-intermediate risk, based on age and the following three pathologic factors:

●The presence of deep myometrial invasion

●Grade 2 or 3 histology

●The presence of lymphovascular space invasion [1]

Women have high-intermediate-risk disease if they are: age ≥70 years with one risk factor, age 50 to 69 years with two risk factors, or age ≥18 years with all three risk factors. We generally use these criteria, except we consider patients whose tumors are grade 3, deeply invasive (at least 50 percent of the myometrium) endometrioid cancers to be high-risk cancers rather than high-intermediate risk, irrespective of the age of the patient or whether other features are present. (See "Adjuvant treatment of high-risk endometrial cancers", section on 'Deeply invasive grade 3 endometrioid carcinoma'.)

In the absence of the criteria for high-intermediate risk, all others are considered to have low intermediate-risk endometrial cancer. In the Gynecologic Oncology Group trial 99 (GOG-99), two-thirds of all recurrences were in women who met these pathologic criteria [1].

By contrast, the Post-Operative Radiation Therapy in Endometrial Cancer (PORTEC) trials define high-intermediate risk by two of three clinicopathologic factors present: age >60 years, outer one-half myometrial invasion, and grade 3 histology [2-4]. In the PORTEC-1 trial, women who underwent observation had a higher rate of relapse in the pelvis if these criteria were met [5]. Notably, the highest-risk groups for recurrence (eg, grade 3, outer one-half myometrial invasion) were not eligible for treatment on this trial. (See 'Is there a role for adjuvant chemotherapy?' below.)

LOW-INTERMEDIATE-RISK DISEASE — For women with low-intermediate-risk disease, we suggest observation only rather than adjuvant radiation therapy (RT) or adjuvant chemotherapy. Given the overall good prognosis of these patients following surgical treatment, there is very little benefit to be gained from adjuvant RT or chemotherapy.

The lack of benefit of adjuvant RT was demonstrated in Gynecologic Oncology Group trial 99 (GOG-99), which randomly assigned 448 women with intermediate-risk endometrial cancer to observation or adjuvant pelvic RT [1]. Among patients with low-intermediate-risk disease, at 48 months, adjuvant pelvic RT resulted in the following outcomes, relative to observation:

●Trends towards lower cumulative recurrence rates (6 versus 2 percent; hazard ratio [HR] 0.46, 90% CI 0.19-1.11) and isolated local recurrence rates (5 versus 0 percent) that did not reach statistical significance. The rates of distant recurrence were similar (1.5 versus 1.4 percent; HR 1.28, 95% CI 0.42-3.85).

●Similar risk of death due to endometrial cancer (HR for mortality 1.04, 90% CI 0.56-1.93). However, the overall incidence of death was low (3 versus 2 percent, respectively).

●Higher rates of moderate to serious (grade 2 to 4) toxicity, including hematologic (14 versus 5 percent), gastrointestinal (64 versus 5 percent), and cutaneous toxicity (15 versus 9 percent). There were also six patients treated with RT who experienced a serious gastrointestinal obstruction compared with one patient in the observation arm.

Chemotherapy has not been evaluated in this subset, given the risks of this treatment and overall good prognosis of patients with low-intermediate-risk disease.

HIGH-INTERMEDIATE-RISK DISEASE

Radiation therapy

Rationale — For women with high-intermediate-risk disease, we suggest adjuvant radiation therapy (RT) following surgery rather than observation. RT can reduce the risk of a recurrence, although it does not appear to improve overall survival (OS). We suggest it for disease that is high intermediate risk, but not low intermediate risk, given higher baseline risk of recurrence and therefore higher absolute likelihood of benefit.

The benefit of adjuvant RT for lowering the risk of a recurrence was demonstrated in Gynecologic Oncology Group trial 99 (GOG-99) [1]. Among those with high-intermediate-risk disease, pelvic RT resulted in a reduction in the cumulative risk of recurrence at 48 months relative to observation (27 versus 13 percent; hazard ratio [HR] 0.42, 90% CI 0.21-0.83), and a trend toward decreased local recurrences (5 versus 13 percent; HR 0.37, 90% CI 0.12-1.11). Despite this, there was no statistically significant reduction in the risk of death (HR 0.73, 90% CI 0.43-1.26), although the study was not powered sufficiently for this endpoint.

Because of the apparent lack of a significant OS advantage with adjuvant RT, some experts prefer not to administer adjuvant RT in this population. However, others prefer to administer adjuvant chemotherapy. The role of chemotherapy or concomitant chemotherapy plus RT specifically for women with intermediate-risk endometrial cancer is discussed below.

VBT preferred over pelvic RT — We suggest vaginal brachytherapy (VBT) for most women with high-intermediate-risk endometrial cancer, rather than pelvic radiation therapy (RT). While VBT and pelvic RT both decrease the risk of a local recurrence, pelvic RT is associated with more toxicity, including long-term urinary and bowel symptoms [3,6-10].

However, we consider patients with deeply invasive, grade 3 endometrioid carcinoma to have high-risk disease, and the approach to such patients is discussed elsewhere. (See "Adjuvant treatment of high-risk endometrial cancers", section on 'Invasive stage IA, IB, or II disease'.)

Intensity-modulated RT (IMRT) is an attractive alternative to VBT, but is not yet widely available. A discussion on the technical aspects of RT for endometrial cancer is covered separately. (See 'IMRT' below and "Radiation therapy techniques in cancer treatment".)

In the Post-Operative Radiation Therapy in Endometrial Cancer (PORTEC)-2 trial, 427 women with high-intermediate-risk disease were randomly assigned treatment with VBT or pelvic RT [3]. At 45 months, there were no statistically significant differences between VBT and pelvic RT in terms of:

●Locoregional recurrence rate (5 versus 3 percent for VBT and pelvic RT, respectively)

●Distant metastases (8 versus 6 percent, respectively)

●Five-year disease-free survival (83 versus 78 percent, respectively) and OS (85 versus 80 percent, respectively)

VBT was associated with a significantly lower rate of treatment-related diarrhea and other bowel symptoms (13 versus 54 percent, respectively). In longer-term follow-up (seven years), patients receiving pelvic RT reported more bowel symptoms with impact on daily activities, and a trend for more urinary symptoms, although impact on overall quality of life was not affected [11].

Vaginal cuff brachytherapy is typically accomplished using high-dose-rate therapy with an iridium-192 source, but also can be delivered using a low-dose rate. Treatment is initiated three to six weeks following surgery, although some experts prefer to wait up to nine weeks to reduce the risk of vaginal cuff dehiscence. VBT consists of three to five fractions given once or twice weekly on an outpatient basis. In general, the upper one-half to upper two-thirds of the vagina is treated; either vaginal ovoids or a vaginal cylinder can be used as applicators (picture 1). The prescription dose depends upon the number of fractions and dose specification point (to the vaginal mucosa or to a depth of 5 mm), and several published fractionation schedules are accepted. One of the more common dose fractionation schedules employed is three once-weekly fractions of 7 Gy each, delivered to a depth of 5 mm from the vaginal mucosal surface.

Possible alternatives

Pelvic RT — Given toxicity considerations, VBT is our preferred approach rather than pelvic radiation therapy (RT) for most patients with high-intermediate-risk endometrial cancer, although pelvic RT is a reasonable alternative if VBT is not available. (See 'VBT preferred over pelvic RT' above.)

However, note that we consider deeply invasive grade 3 endometrioid carcinoma to be high-risk disease, and the approach to such patients is discussed elsewhere. (See "Adjuvant treatment of high-risk endometrial cancers", section on 'Invasive stage IA, IB, or II disease'.)

As demonstrated in the PORTEC trial, pelvic RT resulted in a significant reduction in the risk of a locoregional recurrence compared with surgery alone (5 versus 14 percent, respectively) [12]. However, pelvic RT is associated with both early and late complications [1,13,14]. Early gastrointestinal (GI) side effects (eg, diarrhea or rectal bleeding) may occur in up to 60 percent of women treated with pelvic RT, and severe (grade 3/4) complications can be seen in up to 8 percent of patients. In addition, in the PORTEC study, the rate of late complications (predominantly affecting the GI and urinary systems) was significantly higher in the group treated with RT compared with those who underwent observation (26 versus 4 percent) [4]. (See 'VBT preferred over pelvic RT' above.)

If VBT is not available, for whatever reason, pelvic RT may be used as an appropriate alternative. Planning and delivery techniques for pelvic RT require the use of a standard four-field beam arrangement. Care should be taken to ensure that the vaginal cuff and all locoregionally-draining lymphatics are included in the treatment fields. The typical dose in this setting is 45 to 50.4 Gy given in 1.8 to 2.0 Gy fractions over five to six weeks. Treatment generally is initiated six weeks after surgery to allow for adequate wound healing.

IMRT — Concerns about long-term toxicities and the lack of a survival advantage with pelvic RT in women with intermediate-risk endometrial cancer have led to exploration of alternative modalities of treatment, such as intensity-modulated RT (IMRT). Unlike conventional RT, the prescription dose used in IMRT is conformed to the target tissue in three dimensions, thereby reducing the dose of RT delivered to normal surrounding tissue. Experience with IMRT thus far has been promising, with low rates of both acute and chronic toxicity [15-18]. However, its use is limited to centers specialized in IMRT. (See "Radiation therapy techniques in cancer treatment", section on 'Intensity-modulated radiation therapy'.)

Is there a role for adjuvant chemotherapy? — For most patients with high-intermediate-risk endometrial carcinoma, we do not suggest adjuvant chemotherapy, either alone or in combination with radiation [19-26]. There are only low-quality data that adjuvant chemotherapy is an alternative to RT in women with high-intermediate-risk endometrial cancer to justify the morbidity of treatment [27]. However, we consider deeply invasive cancers that are grade 3 to be high risk, and, in such cancers, chemotherapy (with or without VBT) or pelvic RT are appropriate options.

Support for this approach comes from GOG-249, which enrolled patients with high-risk disease, or high-intermediate-risk disease according to GOG criteria (table 3), and found that in this population, VBT with three cycles of carboplatin/paclitaxel chemotherapy had comparable 36-month recurrence-free survival (RFS, both 82 percent) and 36-month OS (88 versus 91 percent) to pelvic RT, but greater acute toxicity [28-30]. Further details of this trial are discussed elsewhere. (See "Adjuvant treatment of high-risk endometrial cancers", section on 'Invasive stage IA, IB, or II disease'.)

EMERGING MOLECULAR CLASSIFICATION SYSTEMS — There is increasing evidence and understanding of the molecular pathogenesis of endometrial carcinomas which may lead to better prediction of risk of recurrence and prognosis. Data from The Cancer Genome Atlas identified four molecular subtypes: polymerase epsilon (POLE; ultramutated), deficient mismatch repair/microsatellite instability (hypermutated), copy number low (p53wt), and copy number high (TP53 mutated) with prognostic value of prediction of response to treatment and outcomes (table 4).

Given the reproducibility of classification, there is increasing interest in incorporating molecular classification into treatment decision-making. For example, POLE-mutated tumors have been found to have better prognosis. Therefore, in early-stage disease, there is interest in de-escalation of therapy for POLE-mutated endometrial cancer. Incorporation of molecular classification into treatment planning is being looked at prospectively in several large, randomized trials (PORTEC4a and TAPER and the TransPORTEC RAINBO Umbrella Trial). PORTEC4a is an international phase III trial that randomly assigns high-intermediate-risk patients into molecular-integrated risk profile-based adjuvant treatment (observation, vaginal brachytherapy, or external beam pelvic radiation) versus vaginal brachytherapy alone, with primary outcome of vaginal recurrence rates. The TAPER study similarly is focused on de-escalation of therapy with primary outcome of pelvic recurrence. The TransPORTEC RAINBO trial classifies the four molecular subtypes and randomly assigns patients to treatment arms within each one. The paradigm of how we treat high-intermediate-risk endometrial cancer continues to evolve.

UNSTAGED INTERMEDIATE-RISK PATIENTS — Women who did not undergo formal nodal staging as part of their surgery are technically unstaged. For these patients, the data support pelvic radiation therapy (RT) to reduce local recurrences, without re-operation to complete staging [5,31]. (See 'Pelvic RT' above.)

This was demonstrated in the PORTEC study, in which 715 women who had undergone primary surgical therapy (without node dissection) were randomly assigned to observation or to adjuvant treatment with pelvic RT [2,4,5,32]. With a median follow-up of 13 years, the use of pelvic RT resulted in the following outcomes [5]:

●No significant difference in 15-year overall survival compared with observation only (52 versus 60 percent, respectively; p = 0.14).

●A lower locoregional recurrence rate (5 versus 16 percent, hazard ratio with observation 3.46, 95% CI 1.93-6.18), but no statistically significant difference in the rate of distant metastases (9 versus 7 percent).

●There was no statistically significant difference in the rate of second primary cancers at 15 years (22 versus 16 percent; p = 0.10).

PROGNOSIS — Women with low-intermediate-risk endometrial cancer have an excellent prognosis, with recurrence rates of about 5 to 6 percent without any adjuvant therapy. Patients with clinical features that define high-intermediate-risk endometrial cancer have a recurrence risk ranging from 5 (with adjuvant radiation) to 30 percent (if not treated after surgery) [1,2]. However, survival can be expected to be above 80 percent with or without radiation therapy.

POST-TREATMENT SURVEILLANCE — Post-treatment surveillance of women with endometrial cancer is similar regardless of risk. This is discussed in detail separately. (See "Overview of resectable endometrial carcinoma", section on 'Post-treatment considerations'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Uterine cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Endometrial cancer diagnosis, staging, and surgical treatment (Beyond the Basics)" and "Patient education: Endometrial cancer treatment after surgery (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Women with intermediate-risk endometrial cancer are at risk for locoregional relapse. Therefore, many patients undergo adjuvant treatment to reduce risk of recurrences in the pelvis. (See 'Introduction' above.)

●After surgical staging is complete, intermediate-risk endometrial cancer is defined as disease with the following characteristics (algorithm 1):

•Cancer that is not a high-risk histologic type (eg, clear cell, serous, or carcinosarcoma), and is

•Either histologic grade 1 or 2 and invading less than one-half of the myometrium, with lymphovascular invasion;

-Or invading more than one-half of the myometrium (stage IB) or demonstrating occult cervical stromal invasion (stage II);

-Or histologic grade 3 cancer and invading less than one-half of the myometrium. Note that we consider grade 3 endometrioid carcinoma that invades more than one-half of the myometrium to be high risk. (See "Adjuvant treatment of high-risk endometrial cancers", section on 'Deeply invasive grade 3 endometrioid carcinoma'.)

●The Gynecologic Oncology Group (GOG) uses the following risk factors: older age, outer one-half myometrial invasion, grade 2 or 3 differentiation, or the presence of lymphovascular space invasion within the cancer, to determine whether cancers should be considered high-intermediate or low-intermediate risk, according to the table (table 3). While we generally agree with this classification, as mentioned, we consider patients with deeply invasive grade 3 endometrioid carcinomas (T1b or greater) to have high- rather than intermediate-risk disease, irrespective of the presence of other risk factors. (See 'Classification' above and "Adjuvant treatment of high-risk endometrial cancers", section on 'Deeply invasive grade 3 endometrioid carcinoma' and "Adjuvant treatment of high-risk endometrial cancers", section on 'Invasive stage IA, IB, or II disease'.)

●For women without high-risk prognostic factors (ie, low-intermediate-risk disease), we suggest observation over adjuvant radiation therapy (RT) (Grade 2B). (See 'Low-intermediate-risk disease' above.)

●For most women with high-intermediate-risk endometrial cancer, we suggest RT rather than observation alone (Grade 2B). In general, we suggest vaginal brachytherapy rather than pelvic RT (Grade 2B). In general, we suggest not administering adjuvant chemotherapy (Grade 2C), although there may be exceptions for those with multiple risk factors. (See 'High-intermediate-risk disease' above and 'VBT preferred over pelvic RT' above and 'Is there a role for adjuvant chemotherapy?' above.)

●We recommend molecular profiling of tumors into subclassifications (p53, deficient mismatch repair/microsatellite instability, polymerase epsilon, and no specific molecular profile) and utilizing that data to determine appropriate involvement in clinical trials.

●For women with unstaged intermediate-risk endometrial cancer, we suggest pelvic RT rather than observation or repeat surgery for nodal staging (Grade 2C). (See 'Unstaged intermediate-risk patients' above.)

●Post-treatment surveillance of women with endometrial cancer is similar regardless of risk. (See "Overview of resectable endometrial carcinoma", section on 'Post-treatment considerations'.)

Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2004; 92:744.
Creutzberg CL, van Putten WL, Koper PC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet 2000; 355:1404.
Nout RA, Smit VT, Putter H, et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet 2010; 375:816.
Creutzberg CL, van Putten WL, Koper PC, et al. The morbidity of treatment for patients with Stage I endometrial cancer: results from a randomized trial. Int J Radiat Oncol Biol Phys 2001; 51:1246.
Creutzberg CL, Nout RA, Lybeert ML, et al. Fifteen-year radiotherapy outcomes of the randomized PORTEC-1 trial for endometrial carcinoma. Int J Radiat Oncol Biol Phys 2011; 81:e631.
Alektiar KM, Venkatraman E, Chi DS, Barakat RR. Intravaginal brachytherapy alone for intermediate-risk endometrial cancer. Int J Radiat Oncol Biol Phys 2005; 62:111.
Jolly S, Vargas C, Kumar T, et al. Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation for early stage endometrial cancer. Gynecol Oncol 2005; 97:887.
Solhjem MC, Petersen IA, Haddock MG. Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer. Int J Radiat Oncol Biol Phys 2005; 62:1379.
McCloskey SA, Tchabo NE, Malhotra HK, et al. Adjuvant vaginal brachytherapy alone for high risk localized endometrial cancer as defined by the three major randomized trials of adjuvant pelvic radiation. Gynecol Oncol 2010; 116:404.
Becker M, Malafy T, Bossart M, et al. Quality of life and sexual functioning in endometrial cancer survivors. Gynecol Oncol 2011; 121:169.
de Boer SM, Nout RA, Jürgenliemk-Schulz IM, et al. Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial. Int J Radiat Oncol Biol Phys 2015; 93:797.
Creutzberg CL, van Putten WL, Koper PC, et al. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol 2003; 89:201.
Nout RA, Putter H, Jürgenliemk-Schulz IM, et al. Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized PORTEC-2 trial. J Clin Oncol 2009; 27:3547.
Randall ME, Wilder J, Greven K, Raben M. Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma. Int J Radiat Oncol Biol Phys 1990; 19:49.
Beriwal S, Jain SK, Heron DE, et al. Clinical outcome with adjuvant treatment of endometrial carcinoma using intensity-modulated radiation therapy. Gynecol Oncol 2006; 102:195.
Klopp AH, Yeung AR, Deshmukh S, et al. Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203. J Clin Oncol 2018; 36:2538.
Yeung AR, Pugh SL, Klopp AH, et al. Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study. J Clin Oncol 2020; 38:1685.
Wortman BG, Post CCB, Powell ME, et al. Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy. Int J Radiat Oncol Biol Phys 2022; 112:390.
Klopp AH, Jhingran A, Ramondetta L, et al. Node-positive adenocarcinoma of the endometrium: outcome and patterns of recurrence with and without external beam irradiation. Gynecol Oncol 2009; 115:6.
Alvarez Secord A, Havrilesky LJ, Bae-Jump V, et al. The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer. Gynecol Oncol 2007; 107:285.
Frigerio L, Mangili G, Aletti G, et al. Concomitant radiotherapy and paclitaxel for high-risk endometrial cancer: first feasibility study. Gynecol Oncol 2001; 81:53.
Greven K, Winter K, Underhill K, et al. Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer. Gynecol Oncol 2006; 103:155.
Lupe K, D'Souza DP, Kwon JS, et al. Adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field radiation for advanced endometrial cancer. Gynecol Oncol 2009; 114:94.
Onda T, Yoshikawa H, Mizutani K, et al. Treatment of node-positive endometrial cancer with complete node dissection, chemotherapy and radiation therapy. Br J Cancer 1997; 75:1836.
Lupe K, Kwon J, D'Souza D, et al. Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: a sequential approach. Int J Radiat Oncol Biol Phys 2007; 67:110.
Hogberg T, Rosenberg P, Kristensen G, et al. A randomized phase-III study on adjuvant treatment with radiation (RT) ± chemotherapy (CT) in early-stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991). J Clin Oncol 2007; 25S: ASCO #5503.
Susumu N, Sagae S, Udagawa Y, et al. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol 2008; 108:226.
McMeekin DS, Filiaci VL, Aghajanian C, et al. Randomized phase III trial of pelvic radiation therapy (PXRT) versus vaginal cuff brachytherapy followed by paclitaxel/ carboplatin chemotherapy (VCB/C) in patients with high risk (HR), early stage endometrial cancer (EC): a Gynecologic Oncology Group trial. Gynecol Oncol 2014; 134S:438.
Randall M, Filiaci V, McMeekin D, et al. A Phase III Trial of Pelvic Radiation Therapy versus Vaginal Cuff Brachytherapy followed by Paclitaxel/Carboplatin Chemotherapy in Patients with High-risk, Early Stage Endometrial Cancer: A Gynecology Oncology Group Study. Int J Radiat Oncol Biol Phys 99S: ASTRO #LBA-1.
Randall ME, Filiaci V, McMeekin DS, et al. Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer. J Clin Oncol 2019; 37:1810.
Parthasarathy A, Kapp DS, Cheung MK, et al. Adjuvant radiotherapy in incompletely staged IC and II endometrioid uterine cancer. Obstet Gynecol 2007; 110:1237.
Scholten AN, van Putten WL, Beerman H, et al. Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys 2005; 63:834.

Topic 16741 Version 29.0

References

1 : A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study.

2 : Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma.

3 : Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.

4 : The morbidity of treatment for patients with Stage I endometrial cancer: results from a randomized trial.

5 : Fifteen-year radiotherapy outcomes of the randomized PORTEC-1 trial for endometrial carcinoma.

6 : Intravaginal brachytherapy alone for intermediate-risk endometrial cancer.

7 : Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation for early stage endometrial cancer.

8 : Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer.

9 : Adjuvant vaginal brachytherapy alone for high risk localized endometrial cancer as defined by the three major randomized trials of adjuvant pelvic radiation.

10 : Quality of life and sexual functioning in endometrial cancer survivors.

11 : Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial.

12 : Survival after relapse in patients with endometrial cancer: results from a randomized trial.

13 : Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized PORTEC-2 trial.

14 : Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma.

15 : Clinical outcome with adjuvant treatment of endometrial carcinoma using intensity-modulated radiation therapy.

16 : Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203.

17 : Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study.

18 : Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy.

19 : Node-positive adenocarcinoma of the endometrium: outcome and patterns of recurrence with and without external beam irradiation.

20 : The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer.

21 : Concomitant radiotherapy and paclitaxel for high-risk endometrial cancer: first feasibility study.

22 : Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer.

23 : Adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field radiation for advanced endometrial cancer.

24 : Treatment of node-positive endometrial cancer with complete node dissection, chemotherapy and radiation therapy.

25 : Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: a sequential approach.

26 : A randomized phase-III study on adjuvant treatment with radiation (RT)±chemotherapy (CT) in early-stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991)

27 : Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study.

28 : Randomized phase III trial of pelvic radiation therapy (PXRT) versus vaginal cuff brachytherapy followed by paclitaxel/ carboplatin chemotherapy (VCB/C) in patients with high risk (HR), early stage endometrial cancer (EC): a Gynecologic Oncology Group trial

29 : A Phase III Trial of Pelvic Radiation Therapy versus Vaginal Cuff Brachytherapy followed by Paclitaxel/Carboplatin Chemotherapy in Patients with High-risk, Early Stage Endometrial Cancer: A Gynecology Oncology Group Study

30 : Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer.

31 : Adjuvant radiotherapy in incompletely staged IC and II endometrioid uterine cancer.

32 : Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review.

خرید پکیج

Adjuvant treatment of intermediate-risk endometrial cancer

References